tbuckley/cabot-search huggingface dataset:
Perioperative Gabapentin Use and In-Hospital Adverse Clinical Events Among Older Adults After Major Surgery
Authors: Chan Mi Park, Sharon K. Inouye, Edward R. Marcantonio, Eran Metzger, Brian T. Bateman, Jessica J. Lie, Su Been Lee, Raisa Levin, Dae Hyun Kim
Journal: JAMA Internal Medicine (2022)

Gabapentin has been increasingly used as part of a multimodal analgesia regimen to reduce opioid use in perioperative pain management. However, the safety of perioperative gabapentin use among older patients remains uncertain.To examine in-hospital adverse clinical events associated with perioperative gabapentin use among older patients undergoing major surgery.This retrospective cohort study using data from the Premier Healthcare Database included patients aged 65 years or older who underwent major surgery at US hospitals within 7 days of hospital admission from January 1, 2009, to March 31, 2018, and did not use gabapentin before surgery. Data were analyzed from June 14, 2021, to May 23, 2022.Gabapentin use within 2 days after surgery.The primary outcome was delirium, identified using diagnosis codes, and secondary outcomes were new antipsychotic use, pneumonia, and in-hospital death between postoperative day 3 and hospital discharge. To reduce confounding, 1:1 propensity score matching was performed. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were estimated.Among 967 547 patients before propensity score matching (mean [SD] age, 76.2 [7.4] years; 59.6% female), the rate of perioperative gabapentin use was 12.3% (119 087 patients). After propensity score matching, 237 872 (118 936 pairs) gabapentin users and nonusers (mean [SD] age, 74.5 [6.7] years; 62.7% female) were identified. Compared with nonusers, gabapentin users had increased risk of delirium (4040 [3.4%] vs 3148 [2.6%]; RR, 1.28 [95% CI, 1.23-1.34]; RD, 0.75 [95% CI, 0.75 [0.61-0.89] per 100 persons), new antipsychotic use (944 [0.8%] vs 805 [0.7%]; RR, 1.17 [95% CI, 1.07-1.29]; RD, 0.12 [95% CI, 0.05-0.19] per 100 persons), and pneumonia (1521 [1.3%] vs 1368 [1.2%]; RR, 1.11 [95% CI, 1.03-1.20]; RD, 0.13 [95% CI, 0.04-0.22] per 100 persons), but there was no difference in in-hospital death (362 [0.3%] vs 354 [0.2%]; RR, 1.02 [95% CI, 0.88-1.18]; RD, 0.00 [95% CI, -0.04 to 0.05] per 100 persons). Risk of delirium among gabapentin users was greater in subgroups with high comorbidity burden than in those with low comorbidity burden (combined comorbidity index <4 vs ≥4: RR, 1.20 [95% CI, 1.13-1.27] vs 1.40 [95% CI, 1.30-1.51]; RD, 0.41 [95% CI, 0.28-0.53] vs 2.66 [95% CI, 2.08-3.24] per 100 persons) and chronic kidney disease (absence vs presence: RR, 1.26 [95% CI, 1.19-1.33] vs 1.38 [95% CI, 1.27-1.49]; RD, 0.56 [95% CI, 0.42-0.69] vs 1.97 [95% CI, 1.49-2.46] per 100 persons).In this cohort study, perioperative gabapentin use was associated with increased risk of delirium, new antipsychotic use, and pneumonia among older patients after major surgery. These results suggest careful risk-benefit assessment before prescribing gabapentin for perioperative pain management.
Association of State Child Abuse Policies and Mandated Reporting Policies With Prenatal and Postpartum Care Among Women Who Engaged in Substance Use During Pregnancy
Authors: Anna E. Austin, Rebecca B. Naumann, Elizabeth Simmons
Journal: JAMA Pediatrics (2022)

Some states have implemented policies that consider substance use during pregnancy as child abuse and require mandated reporting of substance use during pregnancy. Implications of these policies for health care receipt among pregnant people who engage in substance use are unknown.To examine the association of state child abuse policies and mandated reporting policies with prenatal and postpartum care among women who engaged in substance use during pregnancy.In this cross-sectional study, data from the 2016-2019 Pregnancy Risk Assessment Monitoring System survey were analyzed. The study population included 4155 women from 23 states who reported substance use during pregnancy. Data were analyzed between August and November 2021.Delivery in a state with a child abuse policy only (n = 6), a mandated reporting policy only (n = 4), both policies (n = 7), or neither policy (n = 5). One state switched from a mandated reporting policy only to having both policies.Month of gestation at prenatal care initiation (ie, months 1-10, with a higher number of months indicating later initiation), receipt of adequate prenatal care, and receipt of a postpartum health care visit 4 to 6 weeks after delivery. Sample characteristics were calculated using unweighted frequencies and weighted percentages and means. Associations of state policies with the outcomes were examined using generalized linear regression with generalized estimating equations, adjusting for potential confounders and accounting for the complex sampling design of the Pregnancy Risk Assessment Monitoring System survey.The study sample included 4155 women who reported substance use during pregnancy; 33.9% of these women delivered in states with a child abuse policy only, 16.4% in states with a mandated reporting policy only, 32.9% in states with both policies, and 16.8% in states with neither policy. Overall, 14.7% of women were Black, 69.0% were White, and 64.6% were aged 18 to 29 years at delivery. Women who delivered in states with a child abuse policy only, mandated reporting policy only, or both policies initiated prenatal care at a later month of gestation (β = 0.44 [95% CI, 0.10-0.78], 0.32 [95% CI, 0.04-0.59], and 0.40 [95% CI, 0.09-0.72], respectively) and had a lower likelihood of adequate prenatal care (risk ratio, 0.85 [95% CI, 0.79-0.91], 0.94 [95% CI, 0.87-1.01], and 0.95 [95% CI, 0.89-1.03], respectively) and a postpartum health care visit (risk ratio, 0.89 [95% CI, 0.82-0.96], 0.89 [95% CI, 0.80-0.98], and 0.92 [95% CI, 0.83-1.02], respectively) compared with women who delivered in states with neither policy.The results indicate that state child abuse policies and mandated reporting policies are associated with reduced receipt of prenatal and postpartum care among women who engage in substance use during pregnancy.
Exposure to wildfire-related PM2.5 and site-specific cancer mortality in Brazil from 2010 to 2016: A retrospective study
Authors: Pei Yu, Rongbin Xu, Shanshan Li, Xu Yue, Gongbo Chen, Tingting Ye, Micheline S. Z. S. Coêlho, Paulo H. N. Saldiva, Malcolm R. Sim, Michael J. Abramson, Yuming Guo
Journal: PLoS Medicine (2022)

Background Long-term exposure to fine particles ≤2.5 μm in diameter (PM 2.5 ) has been linked to cancer mortality. However, the effect of wildfire-related PM 2.5 exposure on cancer mortality risk is unknown. This study evaluates the association between wildfire-related PM 2.5 and site-specific cancer mortality in Brazil, from 2010 to 2016. Methods and findings Nationwide cancer death records were collected during 2010–2016 from the Brazilian Mortality Information System. Death records were linked with municipal-level wildfire- and non-wildfire-related PM 2.5 concentrations, at a resolution of 2.0° latitude by 2.5° longitude. We applied a variant difference-in-differences approach with quasi-Poisson regression, adjusting for seasonal temperature and gross domestic product (GDP) per capita. Relative risks (RRs) and 95% confidence intervals (CIs) for the exposure for specific cancer sites were estimated. Attributable fractions and cancer deaths were also calculated. In total, 1,332,526 adult cancer deaths (age ≥ 20 years), from 5,565 Brazilian municipalities, covering 136 million adults were included. The mean annual wildfire-related PM 2.5 concentration was 2.38 μg/m 3 , and the annual non-wildfire-related PM 2.5 concentration was 8.20 μg/m 3 . The RR for mortality from all cancers was 1.02 (95% CI 1.01–1.03, p &lt; 0.001) per 1-μg/m 3 increase of wildfire-related PM 2.5 concentration, which was higher than the RR per 1-μg/m 3 increase of non-wildfire-related PM 2.5 (1.01 [95% CI 1.00–1.01], p = 0.007, with p for difference = 0.003). Wildfire-related PM 2.5 was associated with mortality from cancers of the nasopharynx (1.10 [95% CI 1.04–1.16], p = 0.002), esophagus (1.05 [95% CI 1.01–1.08], p = 0.012), stomach (1.03 [95% CI 1.01–1.06], p = 0.017), colon/rectum (1.08 [95% CI 1.05–1.11], p &lt; 0.001), larynx (1.06 [95% CI 1.02–1.11], p = 0.003), skin (1.06 [95% CI 1.00–1.12], p = 0.003), breast (1.04 [95% CI 1.01–1.06], p = 0.007), prostate (1.03 [95% CI 1.01–1.06], p = 0.019), and testis (1.10 [95% CI 1.03–1.17], p = 0.002). For all cancers combined, the attributable deaths were 37 per 100,000 population and ranged from 18/100,000 in the Northeast Region of Brazil to 71/100,000 in the Central-West Region. Study limitations included a potential lack of assessment of the joint effects of gaseous pollutants, an inability to capture the migration of residents, and an inability to adjust for some potential confounders. Conclusions Exposure to wildfire-related PM 2.5 can increase the risks of cancer mortality for many cancer sites, and the effect for wildfire-related PM 2.5 was higher than for PM 2.5 from non-wildfire sources.
c-MAF coordinates enterocyte zonation and nutrient uptake transcriptional programs
Authors: Alejandra González-Loyola, Jeremiah Bernier-Latmani, Irena Roci, Tania Wyss, Jakob Langer, Stephan Durot, Olivia Munoz, Borja Prat-Luri, Mauro Delorenzi, Matthias P. Lutolf, Nicola Zamboni, Grégory Verdeil, Tatiana V. Petrova
Journal: The Journal of Experimental Medicine (2022)

Small intestinal villi are structural and functional units present in higher vertebrates and uniquely adapted to nutrient absorption. Villus enterocytes are organized in transcriptional "zones" dedicated to specialized tasks such as absorption of specific nutrients. We report that the transcription factor c-MAF is expressed in differentiated lower and mid-villus enterocytes and is a target of BMP signaling. Maf inactivation perturbed the villus zonation program by increasing carbohydrate-related transcripts while suppressing transcripts linked to amino-acid and lipid absorption. The formation of cytoplasmic lipid droplets, shuttling dietary fat to chylomicrons, was impaired upon Maf loss indicating its role in dietary lipid handling. Maf inactivation under homeostatic conditions expanded tuft cells and led to compensatory gut lengthening, preventing weight loss. However, delayed Maf-/- enterocyte maturation impaired weight recovery after acute intestinal injury, resulting in reduced survival. Our results identify c-MAF as a regulator of the intestinal villus zonation program, while highlighting the importance of coordination between stem/progenitor and differentiation programs for intestinal regeneration.
Mandated Reporting of Perinatal Substance Use
Authors: Brownsyne Tucker Edmonds
Journal: JAMA Pediatrics (2022)

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Everolimus-Eluting Stents or Bypass Surgery for Multivessel Coronary Artery Disease: Extended Follow-Up Outcomes of Multicenter Randomized Controlled BEST Trial
Authors: Jung-Min Ahn, Do-Yoon Kang, Sung-Cheol Yun, Seung Ho Hur, Hun-Jun Park, Damras Tresukosol, Woong Chol Kang, Hyuck Moon Kwon, Seung-Woon Rha, Do-Sun Lim, Myung-Ho Jeong, Bong-Ki Lee, He Huang, Young Hyo Lim, Jang Ho Bae, Byung Ok Kim, Tiong Kiam Ong, Sung Gyun Ahn, Cheol-Hyun Chung, Duk-Woo Park, Seung-Jung Park, Jung-Min Ahn, Do-Yoon Kang, Sung-Cheol Yun, Duk-Woo Park, Cheol-Hyun Chung, Seung-Jung Park, Seung Ho Hur, Hun-Jun Park, Damras Tresukosol, Woong Chol Kang, Hyuck Moon Kwon, Do-Sun Lim, Seung-Woon Rha, Myung-Ho Jeong, Bong-Ki Lee, He Huang, Young Hyo Lim, Jang Ho Bae, Byung Ok Kim, Tiong Kiam Ong, Sung Gyun Ahn, Tae-Hyun Yang, Byeong-Keuk Kim, Ji-Yong Jang, Jong-Seon Park, JunBo Ge, Sung Yun Lee, Jun-Hong Kim, Jang-Hyun Cho, Yun Seok Choi, Gyung-Min Park, Robaaya Zambahari
Journal: Circulation (2022)

Background: Long-term comparative outcomes after percutaneous coronary intervention (PCI) with everolimus-eluting stents and coronary artery bypass grafting (CABG) are limited in patients with multivessel coronary artery disease. Methods: This prospective, multicenter, randomized controlled trial was conducted in 27 international heart centers and was designed to randomly assign 1776 patients with angiographic multivessel coronary artery disease to receive PCI with everolimus-eluting stents or CABG. After inclusion of 880 patients (438 in the PCI group and 442 in the CABG group) between July 2008 and September 2013, the study was terminated early because of slow enrollment. The primary end point was the composite of death from any cause, myocardial infarction, or target vessel revascularization. Results: During a median follow-up of 11.8 years (interquartile range, 10.6–12.5 years; maximum, 13.7 years), the primary end point occurred in 151 patients (34.5%) in the PCI group and 134 patients (30.3%) in the CABG group (hazard ratio [HR], 1.18 [95% CI, 0.88–1.56]; P =0.26). No significant differences were seen in the occurrence of a safety composite of death, myocardial infarction, or stroke between groups (28.8% and 27.1%; HR, 1.07 [95% CI, 0.75–1.53]; P =0.70), as well as the occurrence of death from any cause (20.5% and 19.9%; HR, 1.04 [95% CI, 0.65–1.67]; P =0.86). However, spontaneous myocardial infarction (7.1% and 3.8%; HR, 1.86 [95% CI, 1.06–3.27]; P =0.031) and any repeat revascularization (22.6% and 12.7%; HR, 1.92 [95% CI, 1.58–2.32]; P &lt;0.001) were more frequent after PCI than after CABG. Conclusions: In patients with multivessel coronary artery disease, there were no significant differences between PCI and CABG in the incidence of major adverse cardiac events, the safety composite end point, and all-cause mortality during the extended follow-up. Registration: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT05125367 and NCT00997828.
Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis
Authors: Fredrik Piehl, Ann Eriksson-Dufva, Anna Budzianowska, Amalia Feresiadou, William Hansson, Max Albert Hietala, Irene Håkansson, Rune Johansson, Daniel Jons, Ivan Kmezic, Christopher Lindberg, Jonas Lindh, Fredrik Lundin, Ingela Nygren, Anna Rostedt Punga, Rayomand Press, Kristin Samuelsson, Peter Sundström, Oskar Wickberg, Susanna Brauner, Thomas Frisell
Journal: JAMA Neurology (2022)

Rituximab is a third-line option for refractory generalized myasthenia gravis (MG) based on empirical evidence, but its effect in new-onset disease is unknown.To investigate the efficacy and safety of rituximab compared with placebo as an add-on to standard of care for MG.This randomized, double-blind, placebo-controlled study took place throughout 48 weeks at 7 regional clinics in Sweden. Key inclusion criteria were age older than 18 years, onset of generalized symptoms within 12 months or less, and a Quantitative Myasthenia Gravis (QMG) score of 6 or more. Patients were screened from October 20, 2016, to March 2, 2020. Key exclusion criteria included pure ocular MG, suspected thymoma, previous thymectomy, and prior noncorticosteroid immunosuppressants or high doses of corticosteroids.Participants were randomized 1:1 without stratification to a single intravenous infusion of 500 mg of rituximab or matching placebo.Minimal disease manifestations at 16 weeks defined as a QMG score of 4 or less with prednisolone, 10 mg or less daily, and no rescue treatment.Of 87 potentially eligible patients, 25 were randomized to rituximab (mean [SD] age, 67.4 [13.4] years; 7 [28%] female) and 22 to placebo (mean [SD] age, 58 [18.6] years; 7 [32%] female). Compared with placebo, a greater proportion with rituximab met the primary end point; 71% (17 of 24) in the rituximab group vs 29% (6 of 21) in the placebo group (Fisher exact test P = .007; probability ratio, 2.48 [95% CI, 1.20-5.11]). Secondary end points, comparing changes in Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Quality of Life at 16 weeks with QMG at 24 weeks did not differ between groups with censoring for rescue treatment (per-protocol analysis) but were in favor of active treatment when rescue treatment was taken into account by worst rank imputation (post hoc analysis). Rescue treatments were also more frequent in the placebo arm (rituximab: 1 [4%]; placebo, 8 [36%]). One patient in the placebo arm had a myocardial infarction with cardiac arrest and 1 patient in the active arm experienced a fatal cardiac event.A single dose of 500 mg of rituximab was associated with greater probability of minimal MG manifestations and reduced need of rescue medications compared with placebo. Further studies are needed to address long-term benefit-risk balance with this treatment.ClinicalTrials.gov Identifier: NCT02950155.
Novel Temperature‐Sensitive Hydrogel Promotes Wound Healing Through YAP and MEK‐Mediated Mechanosensitivity
Authors: Ze Li, Jinjian Huang, Yungang Jiang, Ye Liu, Guiwen Qu, Kang Chen, Yun Zhao, Peige Wang, Xiuwen Wu, Jianan Ren
Journal: Advanced Healthcare Materials (2022)

Wound healing is a significant problem in clinical management. Various functional dressings are studied to promote wound healing through biochemical factors. They are generally expensive, complex to fabricate, and may adversely affect the wound. Mechanical forces are the critical regulators of tissue repair. Although contraction is shown to promote wound healing, the underlying mechanisms are not fully understood. In this study, a novel adhesive temperature-sensitive mechanically active hydrogel with a simple and inexpensive preparation process is developed. The dressing is able to adhere to the wound surface and actively contract the wound in response to body temperature. This mechanical contraction enhances the proliferative activity of basal cells, reduces the inflammatory response of the wound, and promotes wound healing. Furthermore, RNA-seq clarifies how the gene regulatory network is regulated by contraction. Finally, using pharmacological inhibitors, YAP and MEK are identified as the key signaling molecules for contraction-mediated tissue healing in vivo.
Forecasted 2040 global prevalence of nonalcoholic fatty liver disease using hierarchical bayesian approach
Authors: Michael H. Le, Yee Hui Yeo, Biyao Zou, Scott Barnet, Linda Henry, Ramsey Cheung, Mindie H. Nguyen
Journal: Clinical and Molecular Hepatology (2022)

Background/Aims: Due to increases in obesity and type 2 diabetes, the prevalence of nonalcoholic fatty liver disease (NAFLD) has also been increasing. Current forecast models may not include non-obese NAFLD. Here, we used the Bayesian approach to forecast the prevalence of NAFLD through the year 2040.Methods: Prevalence data from 245 articles involving 2,699,627 persons were used with a hierarchical Bayesian approach to forecast the prevalence of NAFLD through 2040. Subgroup analyses were performed for age, gender, presence of metabolic syndrome, region, and smoking status. Sensitivity analysis was conducted for clinical setting and study quality.Results: The forecasted 2040 prevalence was 55.7%, a three-fold increase since 1990 and a 43.2% increase from the 2020 prevalence of 38.9%. The estimated average yearly increase since 2020 was 2.16%. For those aged &lt;50 years and ≥50 years, the 2040 prevalence were not significantly different (56.7% vs. 61.5%, &lt;i&gt;P&lt;/i&gt;=0.52). There was a significant difference in 2040 prevalence by sex (males: 60% vs. 50%) but the trend was steeper for females (annual percentage change: 2.5% vs. 1.5%, &lt;i&gt;P&lt;/i&gt;=0.025). There was no difference in trends overtime by region (&lt;i&gt;P&lt;/i&gt;=0.48). The increase rate was significantly higher in those without metabolic syndrome (3.8% vs. 0.84%, &lt;i&gt;P&lt;/i&gt;=0.003) and smokers (1.4% vs. 1.1%, &lt;i&gt;P&lt;/i&gt;=0.011). There was no difference by clinical/community setting (&lt;i&gt;P&lt;/i&gt;=0.491) or study quality (&lt;i&gt;P&lt;/i&gt;=0.85).Conclusion: By 2040, over half the adult population is forecasted to have NAFLD. The largest increases are expected to occur in women, smokers, and those without metabolic syndrome. Intensified efforts are needed to raise awareness of NAFLD and to determine long-term solutions addressing the driving factors of the disease.
Impacts of muscle mass dynamics on prognosis of outpatients with cirrhosis
Authors: Tae Hyung Kim, Young Kul Jung, Hyung Joon Yim, Joo Won Baik, Sun Young Yim, Young-Sun Lee, Yeon Seok Seo, Ji Hoon Kim, Jong Eun Yeon, Kwan Soo Byun
Journal: Clinical and Molecular Hepatology (2022)

Sarcopenia negatively affects the prognosis of cirrhotic patients, but clinical implications of changes in muscle mass remain unclear. We aimed to elucidate its role in the prognosis of outpatients with cirrhosis.Patients with cirrhosis who underwent annual abdominal computed tomography (CT) for hepatocellular carcinoma surveillance were included in the prospective cohort. The L3 skeletal muscle index (SMI) was adopted as a proxy for the amount of skeletal muscle, and the rate of SMI change between inclusion and after 1 year (ΔSMI/yr%) was calculated.In total, 595 patients underwent a second CT after 1 year. Among them, 109 and 64 patients had sarcopenia and Child-Pugh class B/C decompensation at inclusion, which changed to 103 and 45 at the 1-year follow-up, respectively. During a median follow-up of 30.1 months after 1 year, 86 patients had at least one cirrhosis complication, and 18 died or received liver transplantation. In the development of cirrhosis complications, ΔSMI/yr% was independently associated, even after adjusting for the Child-Pugh and model for end stage liver disease (MELD)-Na scores. In addition, ΔSMI/yr% showed a good predictive performance for the development of cirrhosis complications within 6 months after 1-year follow-up in all subgroups, with a cut-off of -2.62 (sensitivity, 83.9%; specificity, 74.5%) in the overall population. SMI at 1-year and Child-Pugh score were independent factors associated with survival. In addition, changes in sarcopenia status significantly stratified survival.ΔSMI/yr% was a good predictor of the development of cirrhosis complications in outpatients with cirrhosis, independent of Child-Pugh and MELD scores.